Genetic instability as a basis for transformation of human lymphocytes infected with human retrovirus.

T cell lines (Coculture-14, Coculture-5) derived from human T-cell leukemia virus type I (HTLV-I)-seronegative persons acquired interleukin-2 (IL-2)-dependent continuous growth capacity (immortalized) following in vitro HTLV-I infection. They showed structural abnormalities of chromosomes carrying proviral DNA as seen by in situ hybridization. Following ultraviolet (UV) irradiation, Coculture-5 cells achieved IL-2-independent autonomous growth (transformed) resulting in the establishment of UV-1 and UV-5 lines. They showed additional abnormalities of the same chromosomes. Cocultivation of Coculture-5 cells with IUdR-treated UV-1 cells also resulted in autonomous growth of Coculture-5 cells, giving rise to three cell lines. By ABC immunostaining with specific antibodies, expression of proteins coded for growth regulatory genes, including Ki-67, Topo II, Pol alpha, c-MYC, p53, Rb, bcl-3, bcl-2, and BM-1, was found to be variably altered in transformed cells compared with immortalized cells. These results demonstrated chromosomal instability, altered gene product expression of HTLV-I-infected human lymphocytes, and their susceptibility to transformation without exposure to an initiating carcinogen.